Rituximab in Multirelapsing Minimal Change Disease (MCD) or Focal Segmental Glomerulosclerosis (FSGS)
Status:
Completed
Trial end date:
2011-04-01
Target enrollment:
Participant gender:
Summary
Background. Patients, especially children, with steroid-dependent or multirelapsing nephrotic
syndrome (NS) secondary to minimal change disease (MCD) or idiopathic focal and segmental
glomerulosclerosis (FSGS) on continuous treatment with steroids and/or other
immunosuppressive agents to limit or prevent recurrences are at increased risk of severe
drug-related adverse events. Case reports suggest that Rituximab, a B cell depleting
monoclonal antibody, could be a safe and effective alternative to steroid or
immunosuppressants to achieve and maintain remission in this population.
Objectives. The study is primarily aimed at evaluating whether Rituximab may maintain stable
NS remission after tapering and withdrawal of steroid and immunosuppressive therapy in
patients with MCD or FSGS and steroid-dependent or multirelapsing NS. Secondarily, the study
will assess whether Rituximab allows reducing maintenance doses of steroids and other
immunosuppressants (in those who relapse), thus limiting treatment related side effects and
costs.
Methods. This prospective, sequential, open, study will include 20 patients with histology
evidence of MCD or FSGS and steroid-dependant or multirelapsing NS, who are on stable
complete or partial remission since at least 1 month and, based on their previous history,
are expected to invariably relapse after steroid/immunosuppression withdrawal. After baseline
evaluation of clinical, laboratory and kidney function parameters [including glomerular
filtration rate (GFR), renal plasma flow (RPF), albumin and sodium fractional clearance and
the glomerular albumin permeability assay (Palb)], patients will receive one Rituximab
infusion that will be repeated 1 week later if CD20 cells are not fully depleted from the
circulation. Then ongoing immunosuppression will be progressively tapered up to complete
withdrawal over 6 to 9 months. 24h proteinuria will be monitored monthly and spot urine will
be tested daily by albustix to early detect disease relapses. Baseline evaluations will be
repeated at study end (1 year). Relapses will be treated with high-dose steroids as per
center practice and the last immunosuppressive therapy effective in preventing disease
reactivation will be reintroduced.
Expected results. Rituximab is expected to prevent NS recurrence following tapering and
discontinuation of steroid and other immunosuppressants. Maintaining remission without
chronic immunosuppression is expected to minimize risks and costs of therapy and to
remarkably improve patient outcomes.
Phase:
Phase 3
Details
Lead Sponsor:
Mario Negri Institute for Pharmacological Research